Investigation of Pathogenic to Benign Reclassifications
Distribution of P→B reclassifications across genes and their characteristics.
Temporal patterns in variant reclassifications.
Inferred reasons driving P→B reclassifications based on ACMG evidence codes.
Analysis of submitter patterns in reclassifications.
Complete list of all P→B variants with classification details and inferred reclassification reasons.
Showing all 21 P→B variants sorted by gene and time to benigning. Table is scrollable. The 'inferred_reasons' column shows the likely drivers of reclassification based on ACMG evidence changes.
| gene | variant | type | first_plp_date | first_blb_date | first_plp_submitter | first_blb_submitter | time_to_benign_months | interlab | plp_codes | blb_codes | inferred_reasons |
|---|---|---|---|---|---|---|---|---|---|---|---|
| BRCA2 | NM_000059.4(BRCA2):c.8187G>T (p.Lys2729Asn) | missense | 2002-07-26 | 2011-03-14 | OMIM | Sharing Clinical Reports Project (SCRP) | 103.6 | True | Other/Unknown | ||
| BRCA2 | NM_000059.4(BRCA2):c.7879A>T (p.Ile2627Phe) | missense | 2012-03-11 | 2019-09-01 | Sharing Clinical Reports Project (SCRP) | King Laboratory, University of Washington | 89.7 | True | Other/Unknown | ||
| BRCA2 | NM_000059.4(BRCA2):c.891_899delinsGATACTTAG (p.Thr298_Val300delinsIleLeuArg) | missense | 2017-04-20 | 2023-03-23 | Department of Pathology and Molecular Medicine, Queen's University | University of Washington Department of Laboratory Medicine, University of Washington | 71.1 | True | PM1,PM2,PP4 | BP1 | Guideline/model change |
| BRCA2 | NM_000059.4(BRCA2):c.8851G>T (p.Ala2951Ser) | missense | 2020-04-08 | 2025-05-16 | Center of Medical Genetics and Primary Health Care | Ambry Genetics | 61.2 | True | PM1,PM2,PP3,PP4 | BP2,BP4,BP5,BP7,BS1,BS2,BS3,BS4 | Population frequency, New benign functional evidence, Computational shift |
| BRCA2 | NM_000059.4(BRCA2):c.2623G>C (p.Val875Leu) | missense | 2020-04-08 | 2023-03-23 | Center of Medical Genetics and Primary Health Care | University of Washington Department of Laboratory Medicine, University of Washington | 35.4 | True | BP4,PM1,PM2,PP1,PS1 | BP4,BS1 | Population frequency, Guideline/model change |
| COL4A5 | NM_033380.3(COL4A5):c.2692A>G (p.Met898Val) | missense | 2019-02-14 | 2019-06-15 | Yale Center for Mendelian Genomics, Yale University | PreventionGenetics, part of Exact Sciences | 4.0 | True | Other/Unknown | ||
| HNF1A | NM_000545.8(HNF1A):c.1748G>A (p.Arg583Gln) | missense | 2002-10-01 | 2016-10-27 | OMIM | Ambry Genetics | 168.9 | True | BP1,BP4,BP5,BS1,BS2,BS3,BS4 | Population frequency, New benign functional evidence | |
| HNF1A | NM_000545.8(HNF1A):c.92G>A (p.Gly31Asp) | missense | 2005-03-01 | 2017-03-01 | OMIM | GeneDx | 144.0 | True | BP4,BS1 | Population frequency | |
| NPHS1 | NM_004646.4(NPHS1):c.559G>A (p.Val187Met) | Missense variant in extracellular domain of nephrin protein | 2018-09-16 | 2023-03-02 | Gharavi Laboratory, Columbia University | Labcorp Genetics (formerly Invitae), Labcorp | 53.5 | True | PP4 | Other/Unknown | |
| NPHS1 | NM_004646.4(NPHS1):c.559G>A (p.Val187Met) | missense | 2018-09-16 | 2023-03-02 | Gharavi Laboratory, Columbia University | Labcorp Genetics (formerly Invitae), Labcorp | 53.5 | True | PM2,PP3,PP4 | BA1,BP4,BS1 | Population frequency (BA1 threshold), Computational shift, Guideline/model change |
| NPHS1 | NM_004646.4(NPHS1):c.559G>A (p.Val187Met) | missense | 2018-09-16 | 2023-03-02 | Gharavi Laboratory, Columbia University | Labcorp Genetics (formerly Invitae), Labcorp | 53.5 | True | Other/Unknown | ||
| NPHS2 | NM_014625.4(NPHS2):c.59C>T (p.Pro20Leu) | missense | 2003-05-01 | 2016-03-04 | OMIM | Women's Health and Genetics/Laboratory Corporation of America, LabCorp | 154.1 | True | PM1,PM2,PP1,PS4 | BP4,BP6,BS1,BS2 | Population frequency |
| NPHS2 | NM_014625.4(NPHS2):c.59C>T (p.Pro20Leu) | missense | 2003-05-01 | 2016-03-04 | OMIM | Women's Health and Genetics/Laboratory Corporation of America, LabCorp | 154.1 | True | BS1,BS2 | Population frequency | |
| PAX2 | NM_000278.5(PAX2):c.1058A>C (p.Gln353Pro) | missense | 2020-01-22 | Precision Medicine Center, Zhengzhou University | PreventionGenetics, part of Exact Sciences | NaN | True | PM1,PP1,PP3,PP4,PP5 | BP4,BP7,BS1 | Population frequency, Computational shift, Guideline/model change | |
| PAX2 | NM_000278.5(PAX2):c.1058A>C (p.Gln353Pro) | missense | 2020-01-22 | Precision Medicine Center, Zhengzhou University | PreventionGenetics, part of Exact Sciences | NaN | True | PM1,PP1,PP3,PP4,PP5 | Other/Unknown | ||
| PKD1 | NM_001009944.3(PKD1):c.971G>T (p.Arg324Leu) | missense | 1999-07-01 | 2019-04-19 | OMIM | ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories | 237.6 | True | Other/Unknown | ||
| PKD1 | NM_001009944.3(PKD1):c.971G>T (p.Arg324Leu) | missense | 1999-07-01 | 2019-04-19 | OMIM | ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories | 237.6 | True | Other/Unknown | ||
| RET | NM_020975.6(RET):c.2372A>T (p.Tyr791Phe) | missense | 2006-08-28 | 2012-07-13 | Clinical Molecular Genetics Laboratory, Johns Hopkins All Children's Hospital | Biesecker Lab/Clinical Genomics Section, National Institutes of Health | 70.5 | True | Other/Unknown | ||
| SCNN1G | NM_001039.4(SCNN1G):c.589G>A (p.Glu197Lys) | missense | 2008-05-28 | 2017-04-27 | OMIM | Illumina Laboratory Services, Illumina | 107.0 | True | PP1,PS3 | BP4,BS1 | Population frequency |
| TSC2 | NM_000548.5(TSC2):c.4639G>A (p.Val1547Ile) | missense | 2017-04-11 | 2021-01-19 | OMIM | Ambry Genetics | 45.3 | True | PM2,PP3,PS3 | BP1,BP4,BP5,BS1,BS2,BS3,BS4 | Population frequency, Functional (benign evidence), Computational shift |
| TSC2 | NM_000548.5(TSC2):c.1081C>G (p.Leu361Val) | missense | 2018-08-01 | 2020-03-20 | Liping Wei Laboratory, Peking University | GeneDx | 19.6 | True | BP4,BS4 | Guideline/model change |